Levuglandins (LGs) and isolevuglandins (isoLGs) are a family of reactive oxidized lipids formed by rearrangement of endoperoxide intermediates generated, respectively, through the cyclooxygenase and free radical-induced cyclooxygenation of arachidonates.
The γ-ketoaldehyde functionality of the LGs makes them extraordinarily reactive towards primary amino groups in biolomolecules. LGs and isoLGs react with the ε-amino groups of lysyl residues in proteins to produces covalent adducts with greater avidity than most other lipid oxidation products, e.g., 4-hydroxynonenal (4-HNE) or malondialdehyde (MDA). This feature makes covalent LG/isoLG adducts attractive as biomarkers to evaluate the oxidative injury in the tissues. LGs/isoLGs initially react with the primary amino groups to form Schiff base adducts in seconds, which are transformed to pyrrole adducts in minutes. However, these highly alkylated pyrroles are chemically sensitive compounds in the presence of oxygen and are further oxidized in a few hours to stable end products, lactams and hydroxylactams (HLs). IsoLGE2-protein, iso[4]LGE2-protein and iso[7]LGD2-protein adducts are generated upon oxidation of LDL in vitro. Formation of isoLG protein adducts in vivo has also been confirmed by a variety of immunological and mass spectrometric methods. The levels of isoLG-protein adducts were elevated in diseases associated with oxidative injury.